AbstractPentavalent antimonials, as the 1st choice for the treatment of cutaneous leishmaniasis (CL), have various side effects. Also, there are some reports of drug resistance. Due to its safety, cryotherapy can be a good alternative or complementary treatment in CL. The aim of this study was to explore the possible systemic immunological mechanisms of cryotherapy besides its local effects in the treatment of CL. Twenty patients with CL were selected. The disease was confirmed via a direct smear. A venous blood sample was collected to determine IL-10 and IFN-γ levels before starting cryotherapy. Then, 1 week after 8 sessions of cryotherapy were completed (i.e., 63 d), a 2nd venous sample was taken in order to compare the results with the pretreatment levels of these cytokines using the ELISA method. Cryotherapy resulted in no change in the levels of IL-10 and significantly increased the IFN-γ levels in our patients with CL. Given these inconclusive or even mixed results, a larger sample size is needed in order to better assess the systemic immunological effects of cryotherapy.